Ductus Arteriosus, Patent
Conditions
Keywords
PDA
Brief summary
Patent Ductus Arteriosus is a developmental condition commonly observed among preterm infants. It is a condition where the opening between the two major blood vessels leading from the heart fail to close after birth. In the womb, the opening (ductus arteriosus) is the normal part of the circulatory system of the baby, but is expected to close at full term birth. If the opening is tiny, the condition can be self-limiting. If not, medications/surgery are options for treatment. There are two ways to treat patent ductus arteriosus - one is through closure of the opening with an FDA approved device called PICCOLO, the other is through supportive management (medications). No randomized controlled trials have been done previously to see if one of better than the other. Through our PIVOTAL study, the investigators aim to determine is one is indeed better than the other - if it is found that the percutaneous closure with PICCOLO is better, then it would immediately lead to a new standard of care. If not, then the investigators avoid an invasive costly procedure going forward.
Interventions
DEVICEPercutaneous Patent Ductus Arteriosus Closure (PPC)
Infants in this group will undergo catheter-based PPC closure ≤48 hours following randomization and within 7-days of qualifying ECHO. All participants assigned to PPC will receive the Amplatzer Piccolo™ Occluder which will be implanted within the duct (intraductal placement). The Piccolo™ occluder is approved by the US FDA for this purpose.
COMBINATION_PRODUCTResponsive Management Intervention
Interventional PDA-closure, including PPC or surgical ligation and post-randomization pharmacologic (NSAID or acetaminophen) (enteral or intravenous) PDA treatment, are not allowed unless secondary treatment thresholds (see below) are met. Healthcare decisions for Responsive Management will be made at the discretion of the treatment team, while the infant is carefully monitored for any decline in status that may be attributed to the presence of PDA, in which case, Secondary Intervention (described below) may be considered. Despite widespread acceptance of responsive PDA management, no consensus definition exists. The following Responsive Management interventions are permitted but not required per clinician discretion: 1) fluid restriction between 120-140 mL/kg/day; 2) diuretics (per local practice); 3) increases in positive end-expiratory pressure (PEEP).
DIAGNOSTIC_TESTEchocardiogram, cardiac
An echocardiogram, also known as ECHO, is an ultrasound image of the heart. Echocardiography is a common test used for the diagnosis and management of cardiac diseases or conditions.
Sponsors
National Institutes of Health (NIH)
Abbott
University of Pittsburgh
University of Bristol
Dartmouth College
University of Iowa
Emory University
Cedars-Sinai Medical Center
Children's Hospital Los Angeles
National Heart, Lung, and Blood Institute (NHLBI)
Nationwide Children's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Days to 32 Days
Healthy volunteers
No
Inclusion criteria
1. EPIs born between 22-weeks+0 days (220/7 wks) and 27-weeks+6 days (276/7 wks) gestation, inclusive 2. Admitted to a study NICU 3. Birth weight ≥700-grams 4. Mechanically ventilated at time of consent and randomization 5. HSPDA (PDA Score ≥6) noted on echocardiogram (ECHO) 6. Randomization is able to be performed within 5 days of the qualifying ECHO and when infant is 7-32 days postnatal
Exclusion criteria
Clinical
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of days free of ventilatory support requirement (ventilator-free days; VFDs) | 30 days post-randomization | Ventilator free days (VFDs) are defined as the number of days that a subject is alive and free from mechanical ventilatory support. VFDs are an established respiratory outcome measure in pediatric clinical trials, and are a strong predictor of short-term and longer-term oucomes, including length of neonatal intensive care unit (NICU) stay, morbidities, and mortality. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Diagnosis of pulmonary hypertension or death | 36 weeks post-menstrual age | A compositve binary outcome measure (yes/no), diagnosis of pulmonary hypertension will be determined by cardiac echocardiogram at 36 weeks post-menstrual age. Diagnosis of pulmonary hypertension is an indicator of increased pulmonary vasculature resistance, a marker for increased morbidity and mortality among infants with chronic lung disease. |
| Total days on mechanical ventilation | 4 months corrected age | The total number of days (continuous variable) a study subject requires any use of invasive mechanical ventilatory support within a 24-hour calendar day. |
| Days requiring positive-pressure assisted breathing | Randomization through 4 months corrected age | The sum of days the study subject requires either invasive or non-invasive positive pressure assisted ventilation within a 24 hour calendar day. |
| Days on supplemental oxygen | Randomization through 4 months corrected age | Total number of days the study subject requires supplemental oxygen. The subject may be on either invasive or non-invasive ventilatory support during this time. The subject must be free from supplemental oxygen use for a period of at least 24 hours to interrupt or cease counting. |
| Time to death | Randomization through 4 months corrected age | A continuous measure, in days, of the time from a study subject's randomization to expiration, if this occurs. |
| Diagnosis of cardiac dysfunction | 36 weeks post-menstrual age | A diagnosis of left-ventricular output by echocardiography (ECHO) at 36 weeks post-menstrual age. |
| Abnormal cardiac remodeling | 36 weeks post-menstrual age | Finding of left-ventricular end-diastolic volume (LV EDV) \>97% on echocardiography (ECHO) at 36 weeks post-menstrual age. |
| General Movements Assessment (GMA) | 34 - 36 weeks post-menstrual age | The General Movements Assessment (GMA) is a standardized video-based neurological exam to evaluate the presence of fidgety versus absent fidgety and cramped-synchronized versus non cramped-synchronized movement patterns at 34 - 36 weeks post-menstrual age. It is used to assist in the diagnosis of impaired motor neurodevelopment and cerebral palsy. |
| Need for rescue intervention | Randomization through 4 months corrected age | Recording of incidence of need for study subjects randomized to Responsive Management to undergo Percutaneous Patent Ductus Arteriosus Closure (PPC) due to decline in health status. |
| Hammersmith Neonatal Neurological Examination (HNNE) | 34 - 36 weeks post-menstrual age | The HNNE is a standardized neurological examination of 34 items to evaluate tone, motor patterns, spontaneous movements, reflexes, visual and auditory attention, and behavior. |
| Hammersmith Infant Neurological Examination (HINE) | 3 - 4 months of corrected age | The HINE is similar to the HNNE, used to assess neurological function at 3 - 24 months of age, including cranial nerve function, movements, reflexes, protective reactions and behavior, and age-dependent evaluation of gross and fine-motor function. |
| Positive-pressure dependency or death | 36 weeks post-menstrual age | A composite outcome measure (yes/no), positive pressure dependency at 36 weeks post-menstrual age (PMA) is an indicator of chronic lung disease (CLD), the most common and serious respiratory complication of prematurity. Both invasive and non-invasive positive pressure ventilation at 36 weeks PMA is associated with long-term respiratory and neurodevelopmental impairment. |
| Infant/Toddler Sensory Profile (Sensation Seeking Domain) | 3 - 4 months of corrected age | Caregiver questionnaire responses to determine if their infant is hyposensitive, seeking additional sensory stimulation. There are 6 items with scores of 6 - 30 possible; scores of 7 - 15 are considered Typical performance. |
| Infant/Toddler Sensory Profile (Sensory Sensitivity Domain) | 3 - 4 months of corrected age | Caregiver questionnaire responses to determine if their infant responds readily to sensory stimulation, without actively avoiding it. There are 12 items with scores of 12 - 60 possible; scores of 45 - 57 are considered Typical performance) |
| Infant/Toddler Sensory Profile (Sensation Avoiding Domain) | 3 - 4 months of corrected age | Caregiver questionnaire responses to determine if their infant avoids sensory stimulation. There are 5 items with scores of 5 - 25 possible; scores of 19 - 25 are considered Typical performance. |
| Infant/Toddler Sensory Profile (Low Threshold Domain) | 3 - 4 months of corrected age | Caregiver questionnaire responses which are the sum of the Sensory Sensitivity and Sensation Avoiding domains). Summed scores of 15 - 85 are possible; summed scores of 64 - 81 are considered Typical performance. |
| Baby Care Questionnaire (BCQ) | 3 - 4 months of corrected age | The BCQ is another caregiver-based questionnaire for parental perspectives of an infant's feeding and sleeping habits. It is used as an evaluation of a parent's reliance upon structure / routines and attunement (dependence upon infant's cues). |
| Mother-Infant Bonding Scale (MIBS) | 3 - 4 months of corrected age | The MIBS is an 8-item questionnaire to evaluate a mother's bondedness towards her infant. Responses are scored from 0 to 3 for each item, with a total possible range of 0 - 24. Lower scores indicate more favorable outcomes for mother-infant bondedness, whereas higher scores indicate the potential for difficulties. |
| Type and incidence of any adverse event | 3 - 4 months of corrected age | Reporting of type and frequency of any adverse event that occurs during percutaneous closure procedures, and post-procedurally that may be related to the intervention. |
| Type and incidence of serious adverse event | 3 - 4 months of corrected age | Reporting of type and frequency of any serious adverse event (e.g., potentially life-threatening change in status) that occurs during percutaneous closure procedures, and post-procedurally that may be related to the intervention. |
| Infant/Toddler Sensory Profile (Low Registration Domain) | 3 - 4 months of corrected age | Caregiver questionnaire responses to determine if their infant appropriately processes and responds to environmental stimuli, versus missing or taking longer to respond (Low Registration). There are 13 items with scores of 13 - 65 possible; scores of 42 - 51 are considered Typical performance. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of effect modifiers on primary and secondary outcomes | Birth to 4 months of corrected age | Examination of the homogeneity of the effect of HSPDA on the primary and secondary outcomes will be carried out in statistical analyses using stratification variables (e.g., gender, gestational age, etc.) and characteristics not balanced through random assignment, if any such imbalances are found. |
| Determine whether neurodevelopment at 3-4 months CA is mediated by improved neurodevelopmental profiles at 34-36 weeks PMA. | 34-36 weeks post-menstrual age and 3 - 4 months corrected age | Analysis of HNNE / HINE scores to determine if neurodevelopmental evaluation scores conducted at 34 - 36 weeks post-menstrual age mediate outcomes at 3 - 4 months corrected age |
Countries
United States
Contacts
Primary ContactCarl H Backes
Backup ContactJonathan Slaughter
Outcome results
None listed